A new technique that uses nanoparticles and engineered proteins to broadcast the location of cancer in the body can deliver up to a 40-fold greater concentration of chemotherapy drugs to tumors than untargeted cancer treatments. The new technique, published online yesterday (June 19) in Nature Materials, could inform the development of more efficient therapies that lower required doses and minimize damage to healthy tissues.

“It’s elegant work,” said Mansoor Amiji, co-director of the Nanomedicine Education and Research Consortium at Northeastern University, who was not involved in the research. The system described could eventually open doors to new therapeutic designs for a variety of cancers, he added. “This applies to many different types of systems. It has versatility.”

A big hurdle in improving cancer treatments is the precise targeting of tumors. Restricting radiation therapies to the site of a tumor helps reduce the negative side-effects of less focused treatments, but identifying the tumors' exact location isn't always possible, and such treatments can still damage surrounding tissues. Another approach is to target chemotherapy drugs to tumors using nanoparticles that are attracted to cancerous tissues, but because the liver naturally filters the particles out of the body, large quantities of the therapeutic agent had to be injected in order to see a significant accumulation of the drug at the tumor.

“One of the greatest challenges of direct delivery [of chemotherapy agents] is how to get enough dose to the target," said Amiji. "On average, 50-60 percent of nanoparticles usually end up in the liver."

By designing a system of nanoparticle and protein components that can communicate with one another, biomedical engineer Geoffrey von Maltzahn of Flagship Ventures, an investment firm that helps launch new therapeutics and medical technologies companies, and his colleagues devised a nano-based system that can help localize cancers, as well as more efficiently deliver therapeutic agents to tumors, reducing the potential for collateral damage to healthy tissues.

The system involves two sets of molecular components -- signaling modules, which locate the tumor and trigger the blood in its vessels to coagulate, and receiving modules, which respond to the coagulation and deliver therapeutic agents to the tumors.

The researchers tested the effects of various combinations of signaling and receiving modules on mice with human breast cancer tumors. The signaling modules -- either rod-shaped gold nanoparticles that have previously been shown to gravitate towards cancer, or tissue factor proteins engineered to find tumors undergoing angiogenesis -- traveled through the blood stream and accumulated in the tumors. Once they reached their targets, the engineered proteins bound to specific receptors that directly activated the blood in the nearby vessels to clot. For the gold nanoparticles, the researchers applied near-infrared light to heat the particles and damage the tumor’s blood vessels, triggering coagulation.

The initiation of coagulation then set in motion the second part of the process -- the delivery of drugs or imaging agents by the receiver modules. One receiver the researchers tested, fluorescently-labeled iron oxide nanoparticles coated with peptides that bind to regions of coagulation, acted as an imaging agent to highlight the cancer's location when imaged with an infrared system. The other, liposomes that were also coated with coagulation-seeking peptides, carried the chemotherapy drug doxorubicin to the tumors, which they released upon binding to proteins involved in clotting.

Researchers found that a single treatment with gold nanoparticles and liposomes led to an accumulation of doxorubicin in the tumors that was 40 times more concentrated than was delivered by liposomes not targeted to coagulation, and inhibited tumor growth in mice for the duration of monitoring (24 days), whereas the growth of tumors treated with untargeted liposomes did not slow. Iron oxide receivers paired with either the gold nanorods or the engineered proteins also improved tumor targeting up to 10-fold over iron oxide nanoparticles that were not being directed to tumors by signaling modules. In short, the coordination of the signaling and receiving modules enabled the more efficient delivery of drugs and imaging agents to the cancerous tissues.

“This is the first development of a system of communication between nanoparticles,” said Maltzahn. “This is a step towards thinking of nanoparticles collectively. It is a proof of concept that we hope will lead to the development of therapeutics.”

But inducing coagulation may not be the safest way to target cancer, said Amiji, as blood clots that get swept away in the blood stream could potentially block small vessels. “As long as the clot remains in the tumor, it is okay,” he said. “But if the clots break off, you could risk embolism.”

In addition, because the system is not yet 100 percent accurate, coagulation may be triggered in healthy tissues, or therapeutic agents may be delivered to non-cancerous tissues undergoing normal clotting. "It’s not clear that [coagulation] is the right system to move forward with because the question of specificity is still unclear,” said Maltzahn. Different nanoparticles that utilize different signaling pathways could improve targeting of specific cancer types, he suggested.

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Anonymous

June 21, 2011

This is not a new idea. I submitted patent a few years ago, which describes this process, along with my colleague, Dr. Daniel Murauski. The abstract from that submission "Devices and methods for developing nanospheres thathave bioactive polymer coating to cause thrombosis in various neoplasias andsolid tumors, to assist in micro- and/or molecular-imaging and to enhance theselectivity and exclusivity of drug delivery in the targeted treatment ofspecific disease processes," plainly shows my idea and patent submission (2007) supersedes this current "innovation."Â I also describe this in my doctoral dissertation, "Platelets, Cytoplasts and ECM in the Bioengineering of a 3-Dimensional In Vitro Tumor Model." Can someone at The Scientist please ask Geoffrey von Maltzahn to contact me. If the author of this article (Jessica P. Johnson) can intercede, we be most appreciative.

Thank you, "Ron." I am not someone who deals in opinions, truths, hyperbole, et al. I care only about the facts. In this case, the fact is that I was the first to publish this idea, not the team of authors listed in the Nature Materials article as "Geoffrey von Maltzahn, Ji-Ho Park, Kevin Y. Lin, Neetu Singh, Christian SchwÃ¶ppe, Rolf Mesters, Wolfgang E. Berdel, Erkki Ruoslahti, Michael J. Sailor & Sangeeta N. Bhatia."

With respect, I submit that while it is certainly a validation of my ideas and work that they were able to come to the same conclusions as my own, they did not deserve to receive the credit for something my colleague and I did, first.

I appreciate the restraint you have used in your post. I also would like to see Dr Murauski's response if it is not privileged. Once I was asked to review a manuscript sent to a high impact journal which was nothing but a reprise of my PhD dissertation which was already published it was almost out and out plagiarism. I found it difficult to avoid direct reference to my work in my review. I just pointed out that the information was already in the literature, in several publications.Â I always wondered if that paper would have been published had I not rejected it.

Dr. Easton, this is a very challenging matter and not the first time such a thing has occurred in the history of peer-reviewed publications (far from it!).Â As you have experienced a similar episode, we may count ourselves among the hundreds - over even, thousands - of researchers who have been the victims of plagiarism. Noting that claiming the work of other as one's own does not have to have occurred with any malice of forethought, plagiarism is not only unpleasant, it is irrevocable...

Once someone has been publicly acknowledged as "the" innovator, "the" originator, "the" first observer, "the" discoverer,... it seems to matter not when the actual individual or group of individuals comes forward to lay claim to the ideas or discoveries. The world does not remember these pioneers, for instance:

Thomas Bradwardine, William Heytesbury, John Buridan, Nicole Oresme: all of whom were plagiarized with or without intent by Copernicus, Galileo and Decartes.

I have chosen these very few, relatively obscure geniuses whose mathematical/ theoretical contributions were significant, to point up the ubiquity and regularity of this issue, historically and currently. Any student scientist can conjure the Edisons who may, indeed, have innovated on their own but also claimed the ideas of many, many others who worked under them.

The fact remains that my colleague and I published these ideas first - I, in my dissertation, and Dr. Murauski and I, in our patent submission. It is only reasonable that our ideas receive the attention and acknowledgement deserved. As for Dr. Murauski's comments, I have not yet been able to contact him, regarding the Nature Materials article.

This is not a new idea. I submitted patent a few years ago, which describes this process, along with my colleague, Dr. Daniel Murauski. The abstract from that submission "Devices and methods for developing nanospheres thathave bioactive polymer coating to cause thrombosis in various neoplasias andsolid tumors, to assist in micro- and/or molecular-imaging and to enhance theselectivity and exclusivity of drug delivery in the targeted treatment ofspecific disease processes," plainly shows my idea and patent submission (2007) supersedes this current "innovation."Â I also describe this in my doctoral dissertation, "Platelets, Cytoplasts and ECM in the Bioengineering of a 3-Dimensional In Vitro Tumor Model." Can someone at The Scientist please ask Geoffrey von Maltzahn to contact me. If the author of this article (Jessica P. Johnson) can intercede, we be most appreciative.

Thank you, "Ron." I am not someone who deals in opinions, truths, hyperbole, et al. I care only about the facts. In this case, the fact is that I was the first to publish this idea, not the team of authors listed in the Nature Materials article as "Geoffrey von Maltzahn, Ji-Ho Park, Kevin Y. Lin, Neetu Singh, Christian SchwÃ¶ppe, Rolf Mesters, Wolfgang E. Berdel, Erkki Ruoslahti, Michael J. Sailor & Sangeeta N. Bhatia."

With respect, I submit that while it is certainly a validation of my ideas and work that they were able to come to the same conclusions as my own, they did not deserve to receive the credit for something my colleague and I did, first.

I appreciate the restraint you have used in your post. I also would like to see Dr Murauski's response if it is not privileged. Once I was asked to review a manuscript sent to a high impact journal which was nothing but a reprise of my PhD dissertation which was already published it was almost out and out plagiarism. I found it difficult to avoid direct reference to my work in my review. I just pointed out that the information was already in the literature, in several publications.Â I always wondered if that paper would have been published had I not rejected it.

Dr. Easton, this is a very challenging matter and not the first time such a thing has occurred in the history of peer-reviewed publications (far from it!).Â As you have experienced a similar episode, we may count ourselves among the hundreds - over even, thousands - of researchers who have been the victims of plagiarism. Noting that claiming the work of other as one's own does not have to have occurred with any malice of forethought, plagiarism is not only unpleasant, it is irrevocable...

Once someone has been publicly acknowledged as "the" innovator, "the" originator, "the" first observer, "the" discoverer,... it seems to matter not when the actual individual or group of individuals comes forward to lay claim to the ideas or discoveries. The world does not remember these pioneers, for instance:

Thomas Bradwardine, William Heytesbury, John Buridan, Nicole Oresme: all of whom were plagiarized with or without intent by Copernicus, Galileo and Decartes.

I have chosen these very few, relatively obscure geniuses whose mathematical/ theoretical contributions were significant, to point up the ubiquity and regularity of this issue, historically and currently. Any student scientist can conjure the Edisons who may, indeed, have innovated on their own but also claimed the ideas of many, many others who worked under them.

The fact remains that my colleague and I published these ideas first - I, in my dissertation, and Dr. Murauski and I, in our patent submission. It is only reasonable that our ideas receive the attention and acknowledgement deserved. As for Dr. Murauski's comments, I have not yet been able to contact him, regarding the Nature Materials article.

This is not a new idea. I submitted patent a few years ago, which describes this process, along with my colleague, Dr. Daniel Murauski. The abstract from that submission "Devices and methods for developing nanospheres thathave bioactive polymer coating to cause thrombosis in various neoplasias andsolid tumors, to assist in micro- and/or molecular-imaging and to enhance theselectivity and exclusivity of drug delivery in the targeted treatment ofspecific disease processes," plainly shows my idea and patent submission (2007) supersedes this current "innovation."Â I also describe this in my doctoral dissertation, "Platelets, Cytoplasts and ECM in the Bioengineering of a 3-Dimensional In Vitro Tumor Model." Can someone at The Scientist please ask Geoffrey von Maltzahn to contact me. If the author of this article (Jessica P. Johnson) can intercede, we be most appreciative.

Thank you, "Ron." I am not someone who deals in opinions, truths, hyperbole, et al. I care only about the facts. In this case, the fact is that I was the first to publish this idea, not the team of authors listed in the Nature Materials article as "Geoffrey von Maltzahn, Ji-Ho Park, Kevin Y. Lin, Neetu Singh, Christian SchwÃ¶ppe, Rolf Mesters, Wolfgang E. Berdel, Erkki Ruoslahti, Michael J. Sailor & Sangeeta N. Bhatia."

With respect, I submit that while it is certainly a validation of my ideas and work that they were able to come to the same conclusions as my own, they did not deserve to receive the credit for something my colleague and I did, first.

I appreciate the restraint you have used in your post. I also would like to see Dr Murauski's response if it is not privileged. Once I was asked to review a manuscript sent to a high impact journal which was nothing but a reprise of my PhD dissertation which was already published it was almost out and out plagiarism. I found it difficult to avoid direct reference to my work in my review. I just pointed out that the information was already in the literature, in several publications.Â I always wondered if that paper would have been published had I not rejected it.

Dr. Easton, this is a very challenging matter and not the first time such a thing has occurred in the history of peer-reviewed publications (far from it!).Â As you have experienced a similar episode, we may count ourselves among the hundreds - over even, thousands - of researchers who have been the victims of plagiarism. Noting that claiming the work of other as one's own does not have to have occurred with any malice of forethought, plagiarism is not only unpleasant, it is irrevocable...

Once someone has been publicly acknowledged as "the" innovator, "the" originator, "the" first observer, "the" discoverer,... it seems to matter not when the actual individual or group of individuals comes forward to lay claim to the ideas or discoveries. The world does not remember these pioneers, for instance:

Thomas Bradwardine, William Heytesbury, John Buridan, Nicole Oresme: all of whom were plagiarized with or without intent by Copernicus, Galileo and Decartes.

I have chosen these very few, relatively obscure geniuses whose mathematical/ theoretical contributions were significant, to point up the ubiquity and regularity of this issue, historically and currently. Any student scientist can conjure the Edisons who may, indeed, have innovated on their own but also claimed the ideas of many, many others who worked under them.

The fact remains that my colleague and I published these ideas first - I, in my dissertation, and Dr. Murauski and I, in our patent submission. It is only reasonable that our ideas receive the attention and acknowledgement deserved. As for Dr. Murauski's comments, I have not yet been able to contact him, regarding the Nature Materials article.

I do think the type of plagiarism you and I have experienced is much more disruptive of the social and ethical fabric that binds scientists together than the accidental plagiarism you cite . The first thing that I try to teach my students is good scholarship. With today's web-based NCBI PubMed database , the Web of Science and many other ways to access the literature, there is no excuse for "accidental" plagiarism unless the original research predates indexed publications. One might be inclined to believe that lack of citation of current literature is intentional.

There seems to be no real recourse other than to contact the authors of the offending paper and the journal editor. Of course where patent infringement is concerned legal recourse is available and rather than fight a lawsuit the parties might settle.

I do think the type of plagiarism you and I have experienced is much more disruptive of the social and ethical fabric that binds scientists together than the accidental plagiarism you cite . The first thing that I try to teach my students is good scholarship. With today's web-based NCBI PubMed database , the Web of Science and many other ways to access the literature, there is no excuse for "accidental" plagiarism unless the original research predates indexed publications. One might be inclined to believe that lack of citation of current literature is intentional.

There seems to be no real recourse other than to contact the authors of the offending paper and the journal editor. Of course where patent infringement is concerned legal recourse is available and rather than fight a lawsuit the parties might settle.

I do think the type of plagiarism you and I have experienced is much more disruptive of the social and ethical fabric that binds scientists together than the accidental plagiarism you cite . The first thing that I try to teach my students is good scholarship. With today's web-based NCBI PubMed database , the Web of Science and many other ways to access the literature, there is no excuse for "accidental" plagiarism unless the original research predates indexed publications. One might be inclined to believe that lack of citation of current literature is intentional.

There seems to be no real recourse other than to contact the authors of the offending paper and the journal editor. Of course where patent infringement is concerned legal recourse is available and rather than fight a lawsuit the parties might settle.